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微小 RNA 作为 FOXO 转录因子在癌症管理中的主要调控因子。

MicroRNAs as master regulators of FOXO transcription factors in cancer management.

机构信息

Genome Biology Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India.

Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India; Centre for Pharmacology and Therapeutics, Rosewell Park Comprehensive Care Centre, 665 Elm Street, Buffalo, NY, USA 14203.

出版信息

Life Sci. 2023 May 15;321:121535. doi: 10.1016/j.lfs.2023.121535. Epub 2023 Mar 9.

Abstract

MicroRNAs are critical regulators of the plethora of genes, including FOXO "forkhead" dependent transcription factors, which are bonafide tumour suppressors. The FOXO family members modulate a hub of cellular processes like apoptosis, cell cycle arrest, differentiation, ROS detoxification, and longevity. Aberrant expression of FOXOs in human cancers has been observed due to their down-regulation by diverse microRNAs, which are predominantly involved in tumour initiation, chemo-resistance and tumour progression. Chemo-resistance is a major obstacle in cancer treatment. Over 90% of casualties in cancer patients are reportedly associated with chemo-resistance. Here, we have primarily discussed the structure, functions of FOXO and also their post-translational modifications which influence the activities of these FOXO family members. Further, we have addressed the role of microRNAs in carcinogenesis by regulating the FOXOs at post-transcriptional level. Therefore, microRNAs-FOXO axis can be exploited as a novel cancer therapy. The administration of microRNA-based cancer therapy is likely to be beneficial to curb chemo-resistance in cancers.

摘要

微小 RNA 是大量基因的关键调节因子,包括 FOXO“叉头”依赖转录因子,它们是真正的肿瘤抑制因子。FOXO 家族成员调节细胞凋亡、细胞周期停滞、分化、ROS 解毒和寿命等核心细胞过程。由于多种 microRNAs 的下调,FOXO 在人类癌症中的表达异常,这些 microRNAs 主要参与肿瘤起始、化疗耐药和肿瘤进展。化疗耐药是癌症治疗的主要障碍。据报道,超过 90%的癌症患者的死亡与化疗耐药有关。在这里,我们主要讨论了 FOXO 的结构和功能,以及影响这些 FOXO 家族成员活性的翻译后修饰。此外,我们还讨论了 microRNAs 通过在转录后水平调节 FOXO 在致癌作用中的作用。因此,microRNA-FOXO 轴可以被开发为一种新的癌症治疗方法。microRNA 为基础的癌症治疗的管理可能有利于遏制癌症中的化疗耐药性。

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